CDK5 Inhibitor

(S)-Roscovitine ((S)-Seliciclib; (S)-CYC202) is a potent and cross the blood-brain barrier CDKs inhibitor. (S)-Roscovitine shows neuroprotective efficacy. (S)-Roscovitine has the potential for the research of stroke.

RGB-286638 free base is a potent inhibitor of CDK and MAPK9. RGB-286638 free base inhibits the activities of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3 and p35-CDK5, with IC₅₀ values of 1, 2, 3, 4, 5 and 5 nM, respectively. RGB-286638 free base inhibits GSK-3β and TAK1, with IC₅₀ values of 3 nM and 5 nM, respectively. RGB-286638 free base induces caspase-dependent Apoptosis in cells. RGB-286638 free base delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 free base extends survival in multiple myeloma models. RGB-286638 free base can be used in research related to glioblastoma and multiple myeloma.

Manzamine A hydrochloride, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC₅₀s of 10.2 μM and 1.5 μM, respectively. Manzamine A hydrochloride targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A hydrochloride has antimalarial and anticancer activities. Manzamine A hydrochloride also shows potent activity against HSV-1.

TMX-2039 is a pan-CDK inhibitor for both cell cycle CDKs (CDK1, CDK2, CDK4, CDK5 and CDK6) and transcriptional CDKs (CDK7 and CDK9), with IC₅₀s of 2.6, 1.0, 52.1, 0.5, 35.0, 32.5 and 25 nM, respectively. TMX-2039 acts as a Ligands for Target Protein for PROTACs.

Samuraciclib (CT7001) hydrochloride hydrate is a potent, selective, ATP-competitive and orally active CDK7 inhibitor, with an IC₅₀ of 41 nM. Samuraciclib hydrochloride hydrate displays 45-, 15-, 230- and 30-fold selectivity over CDK1, CDK2 (IC₅₀ of 578 nM), CDK5 and CDK9, respectively. Samuraciclib hydrochloride hydrate inhibits the growth of breast cancer cell lines with GI₅₀ values between 0.2-0.3 μM. Samuraciclib hydrochloride hydrate has anti-tumor effects.

7BIO (7-Bromoindirubin-3-Oxime) is the derivate of indirubin. 7BIO (7-Bromoindirubin-3-Oxime) has inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β). 7BIO (7-Bromoindirubin-3-Oxime) inhibits Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, activation of astrocytes and microglia, and attenuates Aβ oligomer-induced cognitive impairments in mice^[1].

NU6140 is a selective CDK2-cyclin A inhibitor (IC₅₀, 0.41 μM), exhibits 10- to 36-fold selectivity over other CDKs. NU6140 also potently inhibits Aurora A and Aurora B, with IC₅₀s of 67 and 35 nM, respectively. Enhances the apoptotic effect, with anti-cancer activity.

GSK-3 inhibitor 3 is a selective, orally active and brain-penetrant inhibitor of GSK-3, with IC₅₀s of 0.35 nM and 0.25 nM for GSK-3α and GSK-3β, respectively. GSK-3 inhibitor 3 lowers levels of tau protein phosphorylation at S396 in a triple-transgenic mouse Alzheimer’s disease model, with IC₅₀ of 10 nM. GSK-3 inhibitor 3 can be used for neurological disease research.

BS-194 is an orally active, selective and potent CDK inhibitor. BS-194 inhibits CDK2, CDK1, CDK5, CDK7, CDK9 (IC₅₀s: 3, 30, 30, 250, and 90 nM respectively). BS-194 potently inhibits cancer cells proliferation. BS-194 can be used in the research of cancers like breast cancer, colon cancer.

Cdk5i peptide is a CDK5 inhibitory peptide with high binding affinity for Cdk5/p25 (K_d of 0.17 μM), which can block the interaction between CDK5 and p25 and reduce the kinase activity of CDK5/p25. Cdk5i peptide can be used in the stud y of neurodegenerative diseases.

CDK5-IN-1 is a potent CDK5 inhibitor with an IC₅₀ less than 10 nM. CDK5-IN-1 is greater than 100-fold more active against CDK5 than CDK2. CDK5-IN-1 is used for kidney diseases research.

PNU-292137 is an orally active, potent CDK2 inhibitor with IC₅₀s of 37 nM and 92 nM for CDK2/cyclin A and CDK2/cyclin E, respectively. PNU-292137 makes interactions with the hydrophobic pocket at the back of the CDK2 ATP pocket. PNU-292137 efficiently inhibits tumor cell proliferation in human colon and prostate tumor cell lines. PNU-292137 exhibits antitumor activity (TGI>50%) in a mouse xenograft model.

AG-012986 is a pan-CDK inhibitor with K_i values of 44 nM (CDK1), 9.2 nM (CDK4), 94 nM (CDK2), and IC50 values of 22 nM (CDK5), 4 nM (CDK9). AG-012986 causes apoptosis of T-cells by targeting upstream kinases in the p38 Mitogen-activated protein kinase (MAPK) pathway and impairing cellular survival. AG-012986 induces cell cycle arrest, retinoblastoma protein hypophosphorylation, and reduces K_i-67 expression. AG-012986 exerts antiproliferative activity in tumor cells, demonstrates antitumor efficacy in human xenograft models, and causes retinal and peripheral neurotoxicity, plus immune cell toxicity. AG-012986 can be used for the research of colon carcinoma, non-small cell lung carcinoma, lung carcinoma, breast carcinoma, ovarian tumor, pancreatic carcinoma, osteosarcoma, lymphoma, leukemia, retinotoxicity.

GP-82996 (CINK4) is a pharmacological inhibitor of CDK4/6. GP-82996 has IC₅₀s of 1.5, 5.6 and 25 μM for CDK4/cyclin D1, CDK6/cyclin D1 and Cdk5/p35, respectively. GP-82996 induces the apoptosis of cancer cells U2OS. GP-82996 can be used in the research of cancer.

5-Iodo-indirubin-3'-monoxime is a potent GSK-3β, CDK5/P25 and CDK1/cyclin B inhibitor, competing with ATP for binding to the catalytic site of the kinase, with IC₅₀s of 9, 20 and 25 nM, respectively.

NVP-LCQ195 (LCQ-195) is an inhibitor of CDK1/2/3/5/9. NVP-LCQ195 induces cell cycle arrest and eventual apoptotic cell death of multiple myeloma (MM) cells. NVP-LCQ195 triggers decreased amplitude of transcriptional signatures related to oncogenesis, drug resistance and stem cell renewal in MM cell lines.

AT7519 (AT7519M) TFA as a potent inhibitor of CDKs, with IC₅₀s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.

Tambiciclib (GFH009, JSH-009) dimaleate is an orally active, highly potent and selective CDK9 inhibitor (IC₅₀ = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib dimaleate demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib dimaleate can be used for AML research.

BS-181 is a potent and selective CDK7 inhibitor (IC₅₀=21 nM) than Seliciclib (HY-30237). BS-181 is also against CDK2, CDK5 and CDK9 with IC₅₀ values of 880, 3000 and 4200 nM, respectively (fails to block CDK1, 4 and 6). BS-181 inhibits a panel of cancer cells growth (IC₅₀=11.5 μM-37.3 μM) and induces cell apoptosis. BS-181 has the potential for the research of cancer therapy.

(E/Z)-BIO-acetoxime (GSK-3 Inhibitor X) is a potent and selective GSK-3α/β inhibitor, with an IC₅₀ of 10 nM. (E/Z)-BIO-acetoxime shows more than 200-flod selectivity over CDK5/p25, CDK2/cyclin A and CDK1/cyclin B (IC₅₀=2.4, 4.3, 63 μM).